ALK-IN-12 is a highly potent and orally active inhibitor of anaplastic lymphoma kinase (ALK), demonstrating an exceptional IC50 value of 0.18 nM. Additionally, ALK-IN-12 displays inhibitory activity against insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (InsR), with IC50 values of 20.3 nM and 90.6 nM, respectively. Notably, its antitumor effects have been observed, making it a promising compound for targeted cancer therapy.

ALK-IN-12 (compound 11e) effectively reduces the viability of the Karpas-299 ALCL cell line with an inhibition concentration (IC50) of 28.3 nM[1].

Administered orally at doses ranging from 10-50 mg/kg daily for 13 consecutive days, ALK-IN-12 exhibited dose-dependent antitumor activity in a study involving 8-10 week old female SCID/beige mice hosting Karpas-299 xenografts expressing NPM-ALK fusion, achieving tumor stasis at the highest dose of 50 mg/kg. Intravenously given to 6-8 week old female CD rats at 3 mg/kg, ALK-IN-12 displayed pharmacokinetic parameters with an area under the curve (AUC) from time zero to infinity of 3039 ng·h/mL, a clearance (CL) rate of 0.91 h/kg, a half-life (t 1/2) of 6.6 hours, and a steady-state volume of distribution (V ss) of 6.12 L/kg. Similarly, when administered orally at 10 mg/kg to 6-8 week old female CD rats, it showed a maximum concentration (C max) of 3254 ng/mL, an AUC from time zero to infinity of 4056 ng·h/mL, time to reach maximum concentration (t max) of 6.0 hours, a half-life of 12.5 hours, and a bioavailability (F) of 39%.